Modeulation of spasmogen-stimulated Ins(1,4,5)P_3 generation and functional responses by selective inhibitors of types 3 and 4 phosphodiesterase in airways smooth muscle

摘要

The effect of isoenzyme-selective inhibitors of phosphodiesterases PDE3 and PDE4 on cyclic AMP concentration, two indices of phosphoinositide hydrolysis, and contractile responses to spasmogens have been investigated in bovine tracheal smooth muscle (BTSM). Neither the PDE3-selective inhibitor ORG 9935, nor the PDE4-selective inhibitor rolipram increased Cuclic AMP levels in BTSM. However, rolipram addition in the presence of PDE3 inhibition (ORG 9935; 1 μM) concentration-dependently(-log EC_50 (M), 6.55±0.15; n=3) increased cyclic AMP levels to about 70/100 of the maximal response to the β-adrenoceptor agonist isoprenaline.